The proposed work consists of a study of some of the neuroendocrine mechanisms regulating ACTH and TSH secretion. The work includes consideration of cholinergic and monoaminergic systems in the hypothalamus, and their possible effects on pituitary function. The roles of prostaglandins and the adenyl cyclase-cyclic AMP system at both hypothalamic and pituitary levels are of primary interest. There are also studies proposed that deal with the specificity of the action of releasing factors, as well as the interactions between the thyroid and adrenocortical systems at several anatomical levels. Whenever possible, the experiments are to be performed in unanesthetized, unstressed animals. A central theme of the work is to study these endocrine systems as dynamic systems, in that we will be looking at time courses of responses rather than responses at single points in time. Our determination of monoamine turnover rates, as opposed to static concentrations, is also consistent with this theme. The proposed studies will utilize fluorometric assays for corticosterone, norepinephrine, and serotonin; radioimmunoassays for TSH, T4 and T3; and the detemination of adenyl cyclase activity.